Division of Hematology/Oncology, Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
Division of Rheumatology, Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
Aging (Albany NY). 2020 Dec 9;12(24):25939-25955. doi: 10.18632/aging.202167.
Adult hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) ensuring homeostasis of blood production and immune response throughout life. Sex differences in immunocompetence and mortality are well-documented in humans. However, whether HSPCs behave dimorphically between sexes during aging remains unknown. Here, we show that a significant expansion of BM-derived HSPCs occurs in the middle age of female but in the old age of male mice. We then show that a decline of HSPCs in male mice, as indicated by the expression levels of select hematopoietic genes, occurs much earlier in the aging process than that in female mice. Sex-mismatched heterochronic BM transplantations indicate that the middle-aged female BM microenvironment plays a pivotal role in sustaining hematopoietic gene expression during aging. Furthermore, a higher concentration of the pituitary sex hormone follicle-stimulating hormone (FSH) in the serum and a concomitant higher expression of its receptor on HSPCs in the middle-aged and old female mice than age-matched male mice, suggests that FSH may contribute to the sexual dimorphism in aging hematopoiesis. Our study reveals that HSPCs in the BM niches are possibly regulated in a sex-specific manner and influenced differently by sex hormones during aging hematopoiesis.
成体造血干细胞和祖细胞（HSPCs）存在于骨髓（BM）中，可确保终生血液生成和免疫反应的体内平衡。人类的免疫能力和死亡率的性别差异有充分的记录。然而，HSPCs 在衰老过程中是否存在性别差异仍不清楚。在这里，我们表明，雌性小鼠的中年时会出现 BM 来源的 HSPCs 的显著扩增，而雄性小鼠则在老年时出现这种情况。然后我们表明，雄性小鼠 HSPCs 的减少，如选择造血基因的表达水平所示，在衰老过程中比雌性小鼠更早发生。性别错配的异时性 BM 移植表明，中年雌性 BM 微环境在衰老过程中维持造血基因表达中起着关键作用。此外，中年和老年雌性小鼠血清中的垂体促性腺激素卵泡刺激素（FSH）浓度较高，以及 HSPCs 上其受体的表达相应升高，表明 FSH 可能有助于衰老造血中的性别二态性。我们的研究表明，BM 龛中的 HSPCs 可能以性别特异性的方式受到调节，并且在衰老造血过程中受到不同的性激素影响。
